自身免疫性肝炎患者肝组织程序性死亡受体1表达及其临床意义探讨*

目的 观察自身免疫性肝炎（AIH）患者肝组织程序性死亡受体1（PD-1）表达情况及其临床意义。方法 2015年5月~2017年4月我院收治的AIH患者68例（活动期48例,缓解期20例）,在超声引导下使用BARD一次性全自动活检枪行肝穿刺活检术取得肝组织。另选择同期肝血管瘤患者13例,经手术取得肝组织。采用ABC法检测肝组织PD-1表达。比较肝组织PD-1表达情况并采用Pearson相关分析其与血生化学和血清学指标的相关性。结果 48例活动期AIH患者血清TBIL、AST、ALT、ALP和GGT水平分别为（72.1±48.9） μmol/L、（243.1±170.4） U/L、（345.3±217.7） U/L、（154.3±94.6） U/L和（86.5±43.5） U/L,显著高于20例缓解期患者【分别为（14.8±4.2） μmol/L、（28.3±8.7） U/L、（27.6±8.8） U/L、（73.3±51.3） U/L和（71.3±27.3） U/L,P<0.05】;活动期患者血清GLO和IgG水平分别为（34.3±11.3） g/L和（23.2±7.5） g/L,显著高于缓解期【分别为（30.7±10.2） g/L和（11.7±4.6） g/L,P<0.05】; 68例AIH患者肝组织PD-1表达阳性率为（13.61±6.87）%,显著高于对照组的（2.25±0.68）%（P<0.05）,而48例活动期患者肝组织PD-1表达阳性率为（16.56±7.81）%,显著高于缓解期组的（6.56±3.21）%（P<0.05）;48例活动期患者肝组织界面性肝炎为93.75%,淋巴细胞浸润为89.58%,单管破坏性炎症为6.25%,而20例缓解期患者无界面性肝炎、淋巴细胞浸润或单管破坏性炎症表现;活动期AIH患者肝组织PD-1表达阳性率与血清TBIL （r=0.996,P<0.001）、AST（r=0.989,P<0.001）、ALT（r=0.995,P<0.001）、ALP（r=0.998,P<0.001）、GGT（r=0.995,P<0.001）、GLO（r=0.996,P<0.001）和IgG（r=0.997,P<0.001）均呈正相关,在缓解期AIH患者,肝组织PD-1表达阳性率与血清TBIL （r=0.999,P<0.001）、AST（r=0.999,P<0.001）、ALT（r=0.999,P<0.001）、ALP（r=0.999,P<0.001）、GGT（r=0.999,P<0.001）和IgG（r=0.999,P<0.001）呈正相关（P<0.001）。结论 AIH患者肝组织PD-1表达增强,与肝组织炎症活动度密切相关,其参与肝损伤的作用机制还需要进一步探讨。     

恩替卡韦联合硫普罗宁治疗慢性乙型肝炎患者肝功能及其肝纤维化指标的变化

目的 探索硫普罗宁联合恩替卡韦治疗慢性乙型肝炎患者肝功能和肝纤维化指标的变化。 方法 2015年6月~2016年6月我院消化科收治的慢性乙型肝炎患者116例,采用随机数字表法将其分为观察组58例和对照组58例。两组患者均给予口服恩替卡韦治疗,在此基础上,给予观察组口服琉普罗宁治疗,观察12 w。使用普朗牌全自动生化分析仪检测肝功能指标,采用ELISA法检测血清HBV标记物,常规检测血清肝纤维化指标和HBV DNA。 结果 在治疗3 m末,观察组患者血清ALT水平为（41.2±11.7） U/L,显著低于对照组【（49.7±12.4） U/L,P<0.01】,AST水平为（37.2±25.2）U/L,显著低于对照组【（51.3±30.2） U/L,P<0.01】,ALB水平为（35.2±2.5） g/L,与对照组【（35.1±2.7） g/L,P>0.01】比,无显著性差异,TBIL水平为（28.2±6.5）μmol/L,显著低于对照组【（36.5±6.8）μmol/L,P<0.01】;血清HA水平为（93.9±34.2） mg /L,显著低于对照组【（116.5±35.1） mg/L,P<0.01】,LN水平为（103.6±38.2） mg/L,显著低于对照组【（127.9±40.5） mg/L,P<0.01】,C-IV水平为（105.2±40.3） mg/L,显著低于对照组【（133.8±35.1） mg/L,P<0.01】,PCIII水平为（75.3±16.7） mg/L,显著低于对照组【（91.2±18.5） mg/L,P<0.01】;血清HBV DNA转阴率为60.3%,与对照组【60.3%,P>0.05】比,差异无统计学意义,两组均无血清HBsAg转阴或HBeAg转阴;两组均无严重不良反应发生。 结论 硫普罗宁联合恩替卡韦治疗慢性乙型肝炎患者疗效显著,能有效改善肝功能和肝纤维化指标,且使用安全。     

茵栀黄口服液对非酒精性脂肪性肝炎大鼠肝脂肪变的保护作用研究*

目的 探讨茵栀黄口服液对蛋氨酸胆碱缺乏（MCD）饮食诱导的非酒精性脂肪性肝炎（NASH）大鼠肝脂肪变的保护作用。方法 将30只大鼠随机均分为对照组、MCD组和茵栀黄灌胃组。给予对照组普通饮食,给予另两组动物MCD饮食,于第4周末开始分别给予生理盐水或茵栀黄口服液灌胃,第8 w末处死大鼠。取肝组织行病理学检查。取血,使用全自动生化分析仪检测大鼠血清谷丙转氨酶（ALT）、谷草转氨酶 （AST）、总胆红素（TBIL）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、空腹血糖（FBG）。结果 对照组和MCD组大鼠体质量分别为【（487.2±6.5）g和（155.8±3.1）g,P<0.05】,肝指数分别为【（2.92±0.06）%和（5.09±0.19）%,P<0.05】;MCD组大鼠肝组织出现明显的肝脏脂肪变、小叶炎症和气球样变,同时伴有轻度纤维化,茵栀黄处理组大鼠肝指数为（4.47±0.18）%,显著低于MCD组（P<0.05）;茵栀黄组和MCD组大鼠肝组织NAFLD活动度积分（NAS）分别为【（5.9±0.2）分和（7.2±0.1）分,P<0.05】,肝纤维化积分为【（0.3±0.2）分和（0.8±0.2）分,P<0.05】;茵栀黄组和MCD组大鼠血清ALT水平分别为【（68.4±6.4） U/L和（111.9±5.5） U/L,P<0.05】,AST分别为【（110.5±7.9） U/L和（170.5±10.8） U/L,P<0.05】,但是茵栀黄口服液灌胃对MCD大鼠血脂和血糖无显著影响。结论 茵栀黄口服液可以改善MCD诱导的NASH大鼠肝脏脂肪变、肝细胞气球样变、小叶炎症和纤维化,降低NASH大鼠血清转氨酶水平,为应用茵栀黄口服液处理NAFLD提供了实验依据。     

112例妊娠期肝损害患者妊娠结局分析*

目的 分析妊娠期肝损伤对妊娠结局的影响。方法 2013年4月~2018年4月在我院分娩的妊娠期肝损害患者112例和同期分娩但肝功能正常的孕妇50例,分析比较两组分娩情况及母婴妊娠结局。结果 产前,肝损害孕妇血清ALT和AST峰值水平分别为（146.0±46.4） U/L和（112.5±50.1） U/L,产后均恢复正常;肝损害孕妇孕周、新生儿身长和出生60 s Apgar评分与健康孕妇组比,无统计学差异（P>0.05）,而产后出血量为（206.9±80.1） ml,新生儿体质量为（3086.3±252.4） g,与健康孕妇组比,差异显著【分别为（189.8±72.2） ml和（3302.7±320.1）g,P<0.05】;肝损害孕妇羊水性状清所占比例为65.2%,显著低于对照组的82.0%,而羊水Ⅲ度污染、早产、胎膜早破和胎儿宫内窘迫比例分别为23.2%、17.0%、25.9%和18.8%,显著高于对照组的8.0%、2.0%、12.0%和6.0%（P<0.05）。结论 妊娠期肝损害对母婴结局产生负面影响,可增加羊水污染、早产、胎膜早破或胎儿宫内窘迫发生风险。     

利肝隆联合甘草酸二铵治疗自身免疫性肝炎患者疗效及其安全性研究

目的 探讨利肝隆片联合甘草酸二铵胶囊治疗自身免疫性肝炎（AIH）患者的临床疗效。方法 2013年1月~2016年1月我院收治的134例AIH患者被随机分为对照组67例和观察组67例。两组均接受强的松治疗。给予对照组甘草酸二铵胶囊治疗,观察组则在上述治疗基础上加服利肝隆片治疗,均治疗3个月。结果 在治疗3月结束时,观察组ALT、AST、ALP和TBIL水平分别为（52.37±9.29） U/L、（48.36±8.14） U/L、（67.23±3.12） U/L和（16.24±1.24） μmol/L,显著低于对照组（P<0.05）;血清IgG、IgA和IgM水平分别为（11.48±2.12） mg/ml、（2172.14±100.83） mg/L和（2218.48±98.28） mg/L,显著低于对照组（P<0.05）;血清HA、LN和PCⅢ水平分别为（102.24±6.86） μg/ml、（61.43±4.36） μg/mL和（52.46±3.37） μg/ml,显著低于对照组（P<0.05）。结论 利肝隆片联合甘草酸二铵胶囊治疗AIH患者具有较好的临床疗效,值得进行深入研究。     

自拟中药方剂联合水飞蓟宾治疗非酒精性脂肪性肝病患者临床疗效研究

目的 观察自拟中药方剂联合水飞蓟宾治疗非酒精性脂肪性肝病（NAFLD）患者的临床效果。方法 2012年5月~2016年4月我院诊治的NAFLD患者98例,采用随机数字表法分为对照组49例和观察组49例,分别给予水飞蓟宾或水飞蓟宾联合自拟中药方剂治疗,观察3 m。使用流式细胞仪检测外周血调节性T细胞百分比。结果 在治疗3 m末,观察组有效率为98.0%,显著高于对照组的81.6%（P<0.01）;观察组血清ALT、AST和GGT水平分别为38.10±13.92 U/L、42.84±21.9 4U/L和36.07±15.13 U/L,明显低于对照组（59.10±14.23 U/L、63.99±22.51U/L和48.59±13.27 U/L,P<0.01）;观察组TG和TC水平分别为1.28±0.32 mmol/L和4.14±0.64 mmol/L,明显低于对照组（1.83±0.57 mmol/L和5.34±0.51 mmol/L （P<0.05）,但两组调节性T细胞百分比无统计学差异（P>0.05）。结论 自拟中药方剂联合水飞蓟宾治疗NAFLD患者能促进肝功能的改善,降低血脂水平。     

灯盏花素对肝脏缺血再灌注损伤大鼠肝脏和肠黏膜屏障功能的保护作用*

目的 探讨灯盏花素对肝脏缺血再灌注损伤（IRI）大鼠肝脏和肠黏膜屏障功能的保护作用。方法 随机将45只SD大鼠分为对照组、模型组和灯盏花素干预组,制备肝脏缺血再灌注损伤和肠缺血再灌注损伤模型,采用ELISA法检测肠黏膜分泌型（S）IgA和血浆内毒素水平,检测肠组织诱导型一氧化氮合成酶（iNOS）、内皮型一氧化氮合成酶 （eNOS）和一氧化氮（NO）水平,使用试剂盒检测血浆降钙素原（ PCT）、二胺氧化酶（DAO）、TNF-α和IL-1β,采用Western Blotting法检测肝组织Toll样受体-4（TLR4）和核因子（NF）-κB表达水平。结果 模型组大鼠肠粘膜SlgA水平为（0.2±0.1）μg/kg,显著低于对照组【（0.7±0.1）μg/kg,P<0.01】,血清内毒素水平为（0.8±0.1）EU/ml,显著高于对照组【（0.2±0.1） EU/ml,P<0.01】,肠组织iNOS为（0.7±0.1） U/g,显著高于对照组 【（0.2±0.1） U/g,P<0.01】,而eNOS为（0.2±0.1） U/g,显著低于对照组【（0.4±0.1）U/g,P<0.01】, NO为（0.2±0.1）μmol/g,显著低于对照组【（0.4±0.0）μmol/g,P<0.01】, PCT为（5.0±1.2） ng/ml,显著高于对照组【（3.5±0.98）ng/ml,P<0.01】,DAO为（10.5±1.6） Ku/l,显著高于对照组【（6.5±1.2） Ku/l,P<0.01】;灯盏花素干预组SlgA为（0.7±0.1）μg/kg,显著高于模型组【（0.2±0.1）μg/kg,P<0.01】,内毒素为（0.3±0.1） EU/ml,显著低于模型组【（0.8±0.1） EU/ml,P<0.01】,iNOS 为（0.3±0.1） U/g,显著低于模型组 【（0.7±0.1） U/g,P<0.01】, eNOS为（0.8±0.2） U/g,显著高于模型组【（0.2±0.1）U/g,P<0.01】,NO为（0.8±0.1）μmol/g,显著高于模型组【（0.2±0.1）μmol/g,P<0.01】,PCT为（3.9±1.0） ng/ml,显著低于模型组【（5.0±1.2） ng/ml,P<0.01】,DAO为（7.5±1.3） Ku/L,显著低于模型组【（10.5±1.6） Ku/l,P<0.01】;模型组大鼠肝组织TLR4和NF-κB表达及血清TNF-α和IL-1β水平显著高于对照组（P<0.01）,而灯盏花素干预组大鼠肝组织TLR4和NF-κB及血清TNF-α和IL-1β水平显著降低,差异有统计学意义（P<0.01）。结论 灯盏花素通过促进eNOS／NO表达和下调TLR4和NF-κB表达能降低血浆内毒素对肝脏的损伤,对IRI动物具有保护作用。     

恩替卡韦与水飞蓟宾胶囊联合治疗慢性乙型肝炎患者临床效果分析

目的 探讨恩替卡韦与水飞蓟宾胶囊联合治疗慢性乙型肝炎患者的临床效果。 方法 2015年6月~2016年7月我院收治的140例慢性乙型肝炎患者,按照随机分组法将所有患者分为观察组（n=70)和对照组（n=70）。对照组患者口服恩替卡韦片治疗,在观察组,采用恩替卡韦片联合水飞蓟宾胶囊治疗。采用时间分辨免疫荧光法检测血清HBeAg,采用荧光定量PCR法检测血清HBV DNA,采用ELISA法检测血清白细胞介素-6 （IL-6）、TNF-α）和转化生长因子-β （TGF-β,使用FACSCalibur流式细胞仪检测外周血淋巴细胞亚群。 结果 在治疗24 w末,观察组临床症状如乏力、食欲不振、腹胀复常率分别为87.1%、90.0%、82.9%,显著高于对照组的41.4%、71.4%、58.6% （P<0.05）;观察组血清HBeAg和HBV DNA转阴率分别为0.0%和88.6%,与对照组的0.0%和68.6%比,无统计学差异（P>0.05）;观察组血清TBIL、ALT和AST水平分别为（16.49±3.17） μmol/L、（47.36±8.24） U/L和（40.58±5.26） U/L,显著低于对照组的（23.56±3.48） μmol/L、（68.25±7.93） U/L和（66.24±8.24） U/L（P<0.05）;观察组血清IL-6、TNF-α和TGF-β水平分别为（204.8±27.4） μg/L、（68.2±12.5） μg/L和（158.2±15.2） μg/L,显著低于对照组的（264.2±29.2） μg/L、（107.4±13.7） μg/L和（193.5±17.3） μg/L （P<0.05）;观察组外周血CD4+细胞百分比和CD4+/CD8+细胞比值分别为（40.36±3.61）%和（1.50±0.32）,显著高于对照组的【（33.46±3.17） %和（1.33±0.27）,P<0.05】。 结论 恩替卡韦片与水飞蓟宾胶囊联合治疗慢性乙型肝炎患者效果确切,可有效抑制HBV DNA复制,缓解机体炎症反应,提高患者的免疫功能。     

肠内肠外联合营养支持治疗肝细胞癌患者围术期临床研究*

目的 探讨采用肠内肠外联合营养支持对于肝细胞癌（HCC）患者肝叶切除术围手术期的影响。方法 2015年1月~2017年12月在本院行肝叶切除术治疗的HCC患者130例, 在术后根据营养支持方案的不同分为对照组65例和试验组65例, 分别给予肠外营养支持和肠内肠外联合营养支持, 观察术后恢复情况。结果 术后2w, 观察组患者血清白蛋白水平为（41.4±2.9）g/L, 前白蛋白水平为（260.8±12.5）mg/L, Child-Pugh评分为（5.7±1.7）, 与对照组的（34.6±2.5）g/L、（233.3±2.4）mg/L和（6.6±1.5）比, 差异显著（P<0.05）;两组肝功能指标比较, 无显著性差异（P>0.05）;术后, 试验组排便时间为（3.3±1.5）d, 显著早于对照组的【（4.3±1.2）d, P<0.05】, 但住院花费为（53696.3±16754.4）元, 显著多于对照组的（50780.6±13632.7）元（P<0.05）;试验组术后胆瘘、感染和肝功能不全发生率为26.2%, 与对照组的32.2%比, 差异无统计学意义（P>0.05）。结论 在HCC患者接受肝叶切除术的围术期, 采用肠内肠外联合营养支持治疗可以早期促进胃肠运动, 加速康复, 有利于术后恢复。     

自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征：巴黎标准诊断中国患者灵敏度低

目的 评估巴黎标准诊断中国自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征的正确性。方法 回顾性分析按巴黎标准诊断为自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征患者24例和原发性胆汁性肝硬化患者16例的临床资料,对14例部分原发性胆汁性胆管炎患者行肝穿刺检查。结果 16例自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征患者血清TBIL、ALT、GGT和IgG水平分别为（45.3±48.3）μmol/L、（236.8±71.8） U/L、（305.3±258.5） U/L和（25.3±9.9） g/l,与PBC患者【（53.4±57.8）μmol/L、（77.5±71.7） U/L、（389.2±324.3） U/L和（13.9±6.0） g/l,P<0.05】比,差异显著;两组血清ANA、AMA和AMA-M2阳性率无显著性差异（P>0.05）,仅AIH/PBC OS患者血清SMA阳性7例（43.8%）,与PBC组1例（4.2%）比较,差异有统计学意义（P<0.05）;经肝组织学检查,5例原本诊断为PBC患者修正诊断为AIH/PBC OS,他们血清ALT水平分别为40.0U/L、82.8U/L、94.1 U/L、162.1 U/L和117.2 U/L,都远远低于5倍正常值上限。结论 采取巴黎标准诊断中国自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征患者往往因为血清指标水平低而漏诊,及时行肝穿刺检查还是很必要的。     

Autoimmune paediatric liver disease

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis（AIH）,autoimmune sclerosing cholangitis（ASC）,and de novo AIH after liver transplantation.AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody（SMA/ANA,type 1） or liver kidney microsomal antibody（LKM1,type 2）.There is a female predominance in both.LKM1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity,presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both groups.The most common type of paediatric sclerosing cholangitis is ASC.The clinical,biochemical,immunological,and histological presentation of ASC is often indistinguishable from that of AIH type 1.In both,there are high IgG,non-organ specific autoantibodies,and interface hepatitis.Diagnosis is made by cholangiography.Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters,and decreased inflammatory activity on follow up liver biopsies.However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies,hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH postliver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to t     

Clinical usefulness of serum antibodies as biomarkers of gastrointestinal and liver diseases

The progressively growing knowledge of the pathophysiology of a number of immune-mediated gastrointestinal and liver disorders, including autoimmune atrophic gastritis, coeliac disease, autoimmune enteropathy, inflammatory bowel disease, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis and autoimmune pancreatitis, together with the improvement of their detection methods have increased the diagnostic power of serum antibodies. In some cases – coeliac disease and autoimmune atrophic gastritis – they have radically changed gastroenterologists’ diagnostic ability, while in others – autoimmune hepatitis, inflammatory bowel disease and autoimmune pancreatitis – their diagnostic performance is still inadequate. Of note, serum antibody misuse in clinical practice has raised a number of controversies, which may generate confusion in the diagnostic management of the aforementioned disorders. In this review, we critically re-evaluate the usefulness of serum antibodies as biomarkers of immune-mediated gastrointestinal and liver disorders, and discuss their pitfalls and merits.     

Pediatric autoimmune liver disease and extra-hepatic immune-mediated comorbidities

Background

Autoimmune liver disease (AILD) includes autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). AILD is often associated with other extra-hepatic immune-mediated disorders (EDs), but there are few pediatric studies available to date. In this study we evaluated the association between AILD and EDs in our pediatric series.

Clinical analysis of liver transplantation in autoimmune liver diseases

Background: Autoimmune liver diseases(ALDs) consist of autoimmune hepatitis(AIH), primary biliary cirrhosis(PBC), primary sclerosing cholangitis(PSC), Ig G4-associated cholangitis and overlap syndromes.Patients with these diseases may gradually progress to end-stage liver diseases and need liver transplantation. The present study aimed to explore the prognosis of patients with ALDs after liver transplantation.Methods: The clinical data of 80 patients with ALD(24 cases of AIH, 35 of PBC, 15 of PSC and 6 of AIHPBC overlap syndromes) who underwent liver transplantation in Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2004 to September 2016 were collected retrospectively. The causes of death were analyzed and the postoperative cumulative survival rate was estimated by the Kaplan–Meier method. Recurrence and other complications were also analyzed.Results: Of the 80 patients, 18 were males and 62 were females. The average age was 50.5 years and the average Model for End-stage Liver Disease(MELD) score was 14.1. After a median follow-up of 19.8 months, 8 patients died. The 1-, 3-and 5-year cumulative survival rates were all 89.0%. Three cases of recurrent ALDs were diagnosed(3.8%) but they were not totally consistent with primary diseases. Biliary tract complication occurred in 10 patients(12.5%). The new onset of tumor was observed in 1 patient(1.3%). De novo HBV/CMV/EBV infection was found in 3, 8 and 3 patients, respectively.Conclusion: Liver transplantation is an effective and safe treatment for end-stage ALD.     

肝移植术治疗自身免疫性肝炎(附1例报告)

目的探讨肝移植术在自身免疫性肝炎(AIH)中的治疗价值。方法对1例AIH肝硬化患者行肝移植手术。结果患者术后恢复顺利,随访1年未出现排斥反应及复发,抗核抗体(ANA)转阴,肝功能正常。结论肝移植术可作为终末期AIH的有效治疗手段。     

Autoimmune liver diseases and SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry. Here we summarise the current knowledge about auto-immune liver diseases (AILDs) and SARS-CoV-2, focusing on: (1) The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs; (2) the role of SARS-CoV-2 in inducing liver damage and triggering AILDs; and (3) the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver. Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine. Although SARS-CoV-2 infection can lead to the development of several autoimmune diseases, few reports correlate it to the appearance of de novo manifestation of immune-mediated liver diseases such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or AIH/PBC overlap syndrome. Different case series of an AIH-like syndrome with a good prognosis after SARS-CoV-2 vaccination have been described. Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established, these reports suggest that this association could be more than coincidental.     

Paediatric autoimmune liver diseases: A descriptive study of patients from Saudi Arabia

Background and study aimsAutoimmune liver diseases (ALDs) are a clinico-pathologic spectrum of disorders that share some similarities. They are formally classified as autoimmune hepatitis (AIH), isolated autoimmune sclerosing cholangitis (ASC), and the overlap syndrome of these. We describe the clinical, biochemical, and outcomes data of a cohort of autoimmune ALDs patients in a tertiary care centre.Patients and methodsThis is a cross-sectional study conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Data were collected in 2007–2018. All cases were 18 years old or younger at the time of diagnosis. The data collection comprised clinical, laboratory, imaging, treatment, and longitudinal follow-up data.ResultsTwenty-five patients were identified; 14 (56%) were females. Twenty-one patients (84%) had AIH-1,1 patient (4%) had AIH-2, and 3 patients (12%) had autoimmune sclerosing cholangitis (ASC). An insidious course was found in 21 (84%) cases. Acute hepatitis and fulminant hepatic failure was found to be very rare. Eight cases (32%) had cirrhosis at diagnosis. A total of 20 cases (80%) had complete remission following therapy. The median follow-up period was 45 months. There was no mortality, and only one patient was referred for transplant. Thus, the transplant-free survival was 96%.ConclusionsOur study showed predominance of AIH-1 over AIH-2. Response to treatment in our cohort was found to be similar to the results found in some other key studies. Prognosis and transplant-free survival is better than many published paediatric studies.     

Inflammatory pseudotumor of the liver and peripheral eosinophilia in autoimmune pancreatitis

AIM: Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion, the etiology of which remains obscure. It is not associated with any particular diseases apart from phlebitis and Crohn's disease. METHODS: A middle-aged male with hepatic IPT and peripheral eosinophilia associated with autoimmune pancreatitis (AIP) was selected for this study and review of literature. RESULTS: A 59-year-old male was admitted with obstructive jaundice, marked eosinophilia (1 343/mm3) and hypergammaglobulinemia (4 145 mg/dL). Imaging techniques revealed dilatation of the intrahepatic bile duct, stenosis of the common bile duct with diffuse wall thickening, gallbladder wall thickening, irregular narrowing of the pancreatic duct, and swelling of the pancreatic parenchyma. Multiple liver masses were also demonstrated and diagnosed as IPT by biopsy specimens. Six months later, the abnormal features of the biliary tree remarkably improved by the oral administration of prednisolone, and the liver masses disappeared. The swelling of the pancreatic head also improved. The peripheral eosinophil count normalized. IPT associated with AIP, as we know, has not been reported in the literature. The clinical features of the present case mimicked those of pancreatic cancer with liver metastasis. This case deserves to be documented to prevent misdiagnosis of similar cases.     

不同类型自身免疫性肝病患者肝组织炎症因子表达的变化

目的 探讨不同类型自身免疫性肝病(AILD)患者肝组织炎症因子表达的变化。方法 2016年12月～2018年12月我院肝病科收治的AILD患者74例,其中自身免疫性肝炎(AIH)患者19例,原发性胆汁性肝硬化(PBC)患者42例,自身免疫性肝炎/原发性胆汁性肝硬化重叠综合症(AIH/PBC OS)患者13例。采用免疫组化法检测肝穿组织白介素-12(IL-12)、IL-17和干扰素-γ(IFN-γ)表达情况。结果 AIH、PBC和AIH-PBC OS患者血清ALT水平分别为(132.5±12.5)U/L、(40.1±8.4)U/L和(166.2±16.3)U/L,AST水平分别为(120.3±11.7)U/L、(52.8±5.6)U/L和(194.7±18.3)U/L,差异显著(P<0.05);血清ALP水平分别为(98.0±9.2)U/L、(323.5±30.9)U/L和(257.1±24.1)U/L,血清GGT水平分别为(49.1±4.7)U/L、(236.8±22.6)U/L和(376.7±35.5)U/L,差异显著(P<0.05);AIH、PBC和AIH-PBC OS组患者肝组织IL-12表达阳性率无统计学差异(分别为15.8%、7.1%和15.4%,P>0.05),肝组织IL-17阳性表达率无统计学差异(分别为73.7%、76.2%和76.9%,P<0.05),肝组织IFN-γ阳性表达率无统计学差异(分别为68.4%、85.7%和76.9%,P<0.05);AIH患者血清抗肝肾微粒体I型抗体(LKM-1)、抗可溶性肝抗原/肝胰抗原抗体(SLA/LP)阳性率分别为21.1%和10.8%,均显著高于PBC组或AIH-PBC OS患者(分别为0.0%和0.0%,和0.0%和0.0%,P<0.05);PBC患者血清抗sp100抗体阳性率为19.0%,显著高于AIH组(0.0%)或AIH-PBC OS患者(7.7%,P<0.05);AIH-PBC OS组血清抗gp210抗体阳性率为38.5%,显著高于AIH组(0.0%,P<0.05),AIH-PBC OS组患者血清抗线粒体M2抗体(AMA-M2)阳性率为100.0%,显著高于AIH组(0.0%)或PBC组(73.8%,P<0.05);AIH患者血清ANA和SMA阳性率分别为94.7%和78.9%,显著高于PBC患者(分别为19.0%和19.0%,P<0.05)。结论 不同类型AILD患者血清自身抗体呈交叉阳性现象,肝组织炎性因子检测对鉴别诊断没有意义,常规肝功能指标仍对诊断起关键作用。     

自身免疫性肝病的回顾性研究

目的 提高对自身免疫性肝病的认识,以利于早期诊断、早期治疗.方法 回顾性对81例自身免疫性肝病患者进行诊断,比较自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)及其重叠综合征(OS)的临床、血液化学及病理特点.结果 81例患者中,女性占91.4%;总体误诊率为45.7%,OS漏诊率为96.7%,初始诊断为肝硬化者60.5%(49/81),其中37%(30/81)为失代偿期肝硬化.AIH组18.2%(6/33)以急性肝功能衰竭发病,明显高于PBC、OS组,3组患者症状、体征基本一致,AIH、OS组患者丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平及抗核抗体(ANA)阳性率明显高于PBC组(Z=6.411,P=0.041;Z=7.980,P=0.019;X2=11.951,P=0.003),PBC、OS组患者血清门冬氨酸氨基转移酶(GGT)、碱性磷酸酶(ALP)、总胆固醇、载脂蛋白B水平及抗线粒体抗体(AMA)阳性率明显高于AIH组(Z=37.327,P=0.000;Z=12.929,P=0.002;Z=16.722,P=0.000;Z=6.695,P=0.035;X2=31.219,P=0.000).结论 自身免疫性肝病误诊率高.AIH、OS患者氨基转移酶升高明显,ANA阳性率高,PBC、OS患者GGT、ALP升高明显,血脂代谢障碍,AMA阳性率高.